Aberrant D ₁ and D ₃ Dopamine Receptor Transregulation in Hypertension

Abstract

Abstract-Dopamine plays a role in the regulation of blood pressure by inhibition of sodium transport in renal proximal tubules (RPTs) and relaxation of vascular smooth muscles. Key Words: receptors Ⅲ dopamine Ⅲ rats Ⅲ hypertension Ⅲ normotension Ⅲ kidney Ⅲ vascular smooth muscle S everal studies have reported that an impaired renal dopaminergic system may contribute to the pathogenesis of hypertension. 1,2 There is increasing evidence for a direct interaction between D 1 -like and D 2 -like receptors in the kidney. In vitro studies have shown that a D 2 -like receptor, in concert with a D 1 -like receptor, synergistically decreases Na ϩ -K ϩ -ATPase, sodium-phosphate co-transporter, and sodium hydrogen exchanger activities in renal proximal tubule and other cells. [3][4][5] In rats, during conditions of normal sodium load, and especially with increased sodium load, D 1 -like and D 2 -like receptors interact to increase sodium excretion. 1,2,6,7 The D 1 -like receptor interacting with the specific D 2 -like receptor subtype in renal sodium transport is unknown. The 12 We have found that these immortalized RPT cells have characteristics similar to freshly obtained RPTs and RPT brush-border membranes, at least regarding D 1 -like receptors and responses to G-protein stimulation. [13][14][15] The present studies were designed to determine whether D 1 -like receptors regulate D 1 and D 3 receptors and whether the regulation is different in RPT cells from WKY rats and spontaneously hypertensive rats (SHRs).

D 3 Dopamine Receptor Directly Interacts With D 1 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells

“…Our previous studies also showed that the D 1 receptor-mediated stimulation on D 3 receptor expression is impaired in SHR RPT cells. 42 We also found that the costimulation of D 1 -like and D 3 receptors led to additive vasorelaxation in WKY rats but not in SHRs. 42 Luippold et al 47 reported that both expression and function of the renal D 3 receptor are impaired in salt-sensitive Dahl rats as compared with salt-resistant Dahl rats.…”

“…42 We also found that the costimulation of D 1 -like and D 3 receptors led to additive vasorelaxation in WKY rats but not in SHRs. 42 Luippold et al 47 reported that both expression and function of the renal D 3 receptor are impaired in salt-sensitive Dahl rats as compared with salt-resistant Dahl rats. 3,47 In contrast, these investigators did not find a defective response to the intravenous infusion of a D 3 receptor agonist [R(ϩ)-7-hydroxydipropylaminotetralin] in SHRs.…”

“…However, our previous study showed that stimulation of the D 1 receptor increased D 3 receptor protein expression in RPT cells from WKY rats but decreased it in cells from SHRs. 42 We also found that, in RPT cells, activation of the D 1 receptor had no effect on D 3 receptor mRNA levels in WKY but decreased it in SHR cells, indicating that the D 1 -like receptor upregulation of D 3 receptor protein in WKY may be secondary to posttranscriptional or posttranslational (eg, decreased protein degradation) mechanisms, whereas in SHR cells, D 1 -like receptor downregulation of protein expression may occur at the transcriptional or posttranscriptional level (C. Zeng, Z. Yang, P.A. Jose, unpublished data, 2005).…”

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…The AT 1 receptor can also form complexes with the b2 adrenergic receptors, and it is possible to effectively block dual receptor signaling using only a single receptor antagonist (Barki-Harrington et al, 2003). The AT 1 receptor also coimmunoprecipitates with the epidermal growth factor receptor (EGFR); dopamine D1, D3, and D5; and the endothelin B receptors (Zeng et al, 2003a(Zeng et al, ,b, 2005a(Zeng et al, ,b, 2006Olivares-Reyes et al, 2005).…”

The Dopamine Paradox in Lung and Kidney Epithelia

“…For example, the development of hypertension, regardless of its mechanism, is often the result of an altered renal set point for sodium. In this respect, mutations in sodium channels (21) and/or defective hormonal responses (22), as well as abnormal function and regulation of Na ϩ ,K ϩ -ATPase by dopamine, have been described (23,24).…”